Phase I Study of KW-0761 in Relapsed Patients With CCR4-Positive ATL and PTCL

This is a Phase I open-label dose escalation study of KW-0761 in relapsed patients with CCR4 positive Adult T-Cell Leukemia-Lymphoma (ATL) and Peripheral T-Cell Lymphoma (PTCL). This study is designed to evaluate safety, pharmacokinetics, immunogenicity and preliminary efficacy. Enrollment will proceed until a maximum tolerated dose (MTD) and a recommended Phase II dose (RPIID) have been established.

Inclusion criteria

• Histologically confirmed diagnosis of a CCR4-positive ATL and PTCL that is any of the following:

A. ATL (Adult T-Cell Leukemia-Lymphoma)

• Seropositive for anti-Human T-lymphotrophic Virus type-I (HTLV-I) antibody;
• Acute, Lymphoma, or Chronic phase with high-risk factors (within 14 days before the study entry);

B. PTCL (Peripheral T-Cell Lymphoma)

• Includes Mycosis Fungoides and Sezary Syndrome;

2: Relapsed to the latest standard chemotherapy;

3: Received at least one prior chemotherapy;

4: After 4 weeks from a prior therapy;

5: Have measurable disease;

6:Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1;

7: Male or female, at least 20 years and not older than 70 years of age;

8: Signed written informed consent;

9: Stay in hospital for 4 weeks;

10: HBs antigen: negative, HBV-DNA: below the limit of quantification (within 14 days before the study entry);

11: Adequate bone marrow, hepatic and cardiac function including the followings:

• Neutrophil count ≥ 1,500 /mm3,
• Platelets ≥ 75,000 /mm3,
• Hemoglobin ≥ 8.0 g/dL
• Serum creatinine ≤ 1.5 x ULN;
• Serum SGOT (AST) and SGPT (ALT) ≤ 2.5 x ULN (≤ 5.0 x ULN if considered due to disease involvement in liver);
• Serum bilirubin ≤ 1.5 x ULN (≤ 3.0 x ULN if considered due to disease involvement in liver)
• Serum calcium ≤ 11.0 mg/dL
• PaO2 ≥ 65 mmHg or SaO2 ≥ 90%
• No clinically significant Electrocardiogram abnormality
• Left Ventricular Ejection Fraction ≥ 50% [by ECHO or MUGA]

Exclusion criteria

• Co-existing active infection or any co-existing medical condition that may compromise the safety of patients during the study, affect the patient's ability to complete the study, or interfere with interpretation of study results;
• Active tuberculosis;
• Prior stem cell transplantation;
• Myocardial infarction (within 12 months prior to the study entry);
• Concurrent acute or chronic hepatitis, or cirrhosis;
• Anti-HCV: positive, Anti-HIV: positive
• Concurrent active malignant disease;
• Known allergic reaction to antibody therapy;
• Concomitant treatment with systemic steroids;
• Prior and Concurrent psychiatric disorder including dementia, epilepsy or any other CNS diseases;
• Evidence of CNS metastasis at baseline;
• Prior and Concurrent spinal cord disease;
• Radiation therapy for bulky mass disease at the time of study entry or considered to require radiation therapy during the study;
• Female patients who are pregnant or breast feeding;
• Female patients of childbearing potential, unwilling to use an approved, effective means of contraception in accordance with the institution's standards;
• Treatment with any other investigational agent within the 4 months prior to study entry;
• For any reason is judged by the Investigator to be inappropriate for study participation, including an inability to communicate or cooperate with the Investigator.